Delta 5, 16-3-ethylenedioxy-pregnadiene-11, 20-dione and process therefor



A -3ETHYLENEDEGXYEREGNADHENE-lLZii- DKQNE AND PRGCEiiiS THEREFQR Lewis H. Sarett, Princeton, and George I. Poss, North Piainfieid, N. 3., and Wiiiiam F. Johns, Madison, Wis, assignors to Merck & (30., Inc, Railway, N. 5., a corporation of New Jersey No Drawing. Appiication September 9, 1953 Serial No. 379,282

7 Claims. (Cl. 26ii239.55)

This invention relates to novel dodecahydrophenanthrene compounds, and processes of preparing the same. More particularly, it is concerned with a method of forming the 5 membered D ring of the steroid molecule from an appropriately substituted dodecahydrophenanthrene compound, and With the new compounds so obtained. Specifically, it is concerned with a novel method of converting 2,4b-dimethyll- ,B-hydroxyethyl -2-methally-7- ethylenedioxy l,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrenei-ol to 2,4b-dimethyl-7-ethylenedioXy-2- (B-ketopropyl)-1-acetaldehydo l,2,3,4,4a,4b,5,6,7,8,10, 10a-dodecahydrophenanthrene-4-one, and the process of convertingthis compound to 21 -3-ethylenedi0Xy-pregnadiene-lLZO-dione, and the valuable compounds so prepared.

The preparation of valuable steroid substances by total synthesis, involving formation of the four ring system, introduction of angular methyl groups, at positions 10 and 13, and placing of desired functional substituents in the ring system, presents a formidable challenge. In addition to these diificultie's, the problem is further complicated by the stereochemistry of steroidal substances. Thus, saturated steroids, with a minimum of six asymetric centers, are capable of existing in at least sixty four stereochernical modifications. In spite of these dificulties, efforts have been made to prepare steroids by total synthesis in View of the importance and value of steroids such as cortisone, and the scarcity of raw materials suitable as starting materials for the preparation of these important products.

it is an object of the present invention to provide a method of preparing steroid compounds from dodecahydrophenanthrene compounds. Another object is to provide a process for the preparation of l1-keto progesterone from functionally substituted dodecahydrophenanthreue compounds.

An additional object is to provide novel dodecahydrophenanthrene compounds which are useful as intermediates in the synthesis of ll-keto progesterone.

Other objects Will be apparent from the detailed de scription of this invention hereinafter provided.

In accordance with the present invention, it is now found that derivatives of 2,4b-dirnethyl-l-(B-hydroxyethyl)-2-methallyl-1,2,3,4,4a,4b,5,6,7,9,l0,10a dodecahydrophenanthrene-4-ol-7-one wherein the 7-keto substituent is blocked or protected by a substituent convertible to keto by hydrolysis, can be converted into A atent Fatented June 3,

v VI wherein R represents a substituent convertible to a keto group by acid hydrolysis, and R represents a keto-or a hydroXyl group.

In this sequence of reactions the starting material, compound I, is first treated with an oxidizing agent to produce the l-acetaldehydoi-kcto compound, compound H. This compound isthenreactedwith osmium tetroxide and the resulting osmate ester hydrolyzed to convert the methaiiyi substituent at position 2 to a ,8,' -dihydroXyisobutyl substituent, thereby producing compound HI. Upon reacting compound 111 with periodic acid the ,8,'ydihydroxyisobutyl substituent is converted to an fi-keto propyl group to produce compound IV. The ring closure of compound IV to form the five Inembered D ring of the steroid molecule is effected by reacting this compound with an alkali to produce compound V. Upon hydrolyzing compound V with acid, the ethylencdioxy group is cleaved forming a keto group at position 3, and causing the double bond to shift; fromthe 5,6 position to it e 4,5, position, thereby producing compound VI.

- Alternatively, as indicated in the flow sheet above,

compound IV can be prepared directly from compound II. In this method compound II is reacted with ozone and the resulting ozonide reduced to obtain compound IV.

In the reactions described above, the keto group at C-7 of the dodecahydrophenanthrenenucleus is blocked or protected with a group convertible to ketoby hydrolysis.

Thus, the 7-keto group can be blocked by enol ether, ketal, mercaptol, cyclic amine, cyclic ketal, cyclic mercaptol, cyclic hemithioketal groups and the like. Pursuant to a preferred embodiment of our invention, it is found that derivatives of 2,4b-dimethyl-l-(fi-hydroxyethyl)-2-methallyl-1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene-4-ol-7-one or the corresponding 4,7-

-dione wherein the 7-keto substituent is replaced by a cyclic group of the formula wherein R represents a hydrocarbon radical or hydrogen, X represents oxygen or sulfur, and n represents the integer 0 or 1, are most suitable for use as starting materials in our process. Examples of such compounds having a cyclic ketal, mercaptol or hemithioketal group that might be mentioned are 2,4b-dimethyl-l-(B-hydroxyethyl)-2- methallyl 7 ethylenedioxy-l,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-ol, 2,4b dimethyl-l-(fl-hydroxyethyl)-2-methallyl7 ethylenemercaptol 1,2,3,4,4a, 4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-ol, and 2,4b dimethyl-l-(fi-hydroxyethyl)-2-methallyl-7-ethylenehemithioketal 1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-4-ol, or the corresponding 4,7-dione compounds. The 2,4b-dimethyl-1-(B-hydroxyethyl)-2- methallyl 7 ethylenedioxy-l,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-ol can be prepared as described in the copending application of two of us, Serial No. 310,134, now Patent No. 2,786,064, filed September 17,1952. The 2,4b-dimethyl 1 (fi-hydroxyethyD-Z- methallyl 7 ethylenedioxy-1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-one can be prepared by subjecting 2,4b-dimethyl-l-(2 tosyloxyethyl) -2-methallyl-7- ethylenedioxy-l,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene (prepared as described in copending application Serial No. 310,134) to alkaline hydrolysis. The 2,4b-dimethyl-l-(B-hydroxyethyl)-2-methallyl 7 ethylenemercaptol-l,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-ol and 2,4b-dimethyl-1-( fl-hydroxyethyD- 2-methallyl-7-ethylenehemithioketal 1,2,3,4,4a,4b,5,6,7, 8,10,10a-dodecahydrophenanthrene-4-ol can be obtained by reacting 2,4b-dimethyl-1-(fi-hydroxyethyl)-2-methallyl 1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene-4-ol-7-one (prepared as described in copending application Serial No. 310,134) with ethanedithiol and ,B-mercaptoethanol respectively in the presence of fused zinc chloride and anhydrous sodium sulfate. Similarly, the corresponding 4-one compounds can be prepared utilizing the 4,7-dione as the starting material. Although, as indicated above, various substituents can be used to block or protect the 7-keto group, we have found that the cyclic ketal derivatives, and in particular the 7-ethylenedioxy derivative, are most conveniently utilized as the starting material in the processes of our invention.

The ethylenedioxy group of the intermediate products formed in our process, namely, compounds II, III, and IV, is cleaved by hydrolysis with acid, for example by eating with perchloric acid, to produce the corresponding 7-keto compounds. In this hydrolysis, the double bond at the 8a:9 position is shifted to the 8:8a position, thus forming an a ti-unsaturated ketone.

For the purpose of providing a better understanding of this invention, our processes can be exemplified by the application to a specific starting material, the ethylenedioxy derivative of 2,4b-dimethyl-2-methallyl1-(5- hydroxyethyl) 1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrenel-ol-7-one.

In the first step of our process, this starting material, 2,4b-dimethyl 7 ethylenedioxy-Z-methallyl-1-(fi-hydroxyethyl) 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-ol is reacted with an oxidizing agent to convert the 4-hydroxy substituent to a keto group and to convert the 5-hydroxyethyl to the acetaldehydo substituent. We have found that this oxidation is most conveniently accomplished by reacting a solution of the starting material in an organic base with a complex formed by reacting an organic base with chromium trioxide, for example the pyridine-chromium trioxide complex. This method of oxidizing primary and secondary alcohols to the corresponding carbonyl compounds is described in the copending application of one of us, Serial No. 292,985, filed June 11, 1952. Thus, this oxidation is readily effected by intimately contacting a solution of the starting compound in pyridine with the complex formed by reacting chromium trioxide with pyridine and allowing the reaction mixture to stand at room temperature for sufficient time to complete the oxidation. The 2,4b-dimethyl-7-ethylenedioxy-2-methallyl 1 acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-one is recovered by diluting the reaction mixture with water, extracting the aqueous solution with a water immiscible solvent for the product, such as ethyl ether, chromatographing the resulting ether solution over acid-washed alumina, and eluting the product with a mixture of petroleum ether and ethyl ether.

Although the principal product of the oxidation reaction is 2,4b-dimethyl-7-ethylenedioxy 2 methallyl-1- acetaldehydo-1,2,3,4,4a,4b,5,6,7,8,l0,10a dodecahydrophenanthrenet-one, small amounts of other oxidation products such as 2,4b-dimethyl-7-ethy1enedioxy-Z-methallyl 1 (,B-hydroxyethyl)-1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-one and the corresponding l-(carboxymethyl) compound are also obtained. These products can be reduced by reaction with lithium aluminum hydrideto produce an epimeric form of the starting material. This epimeric form of the starting material can be used in the present process as effectively as the original starting compound, thereby increasing the final yield of product.

In the next steps of our process, the Z-methallyl substituent of 2,4b-dimethyl-7-ethylenedioxy-2-methallyl-1- acetaldehydo-l,2,3,4,4a,4b,5,6,7,8,l0,10a dodecahydrophenanthrenei-one is converted to a B-ketopropyl group. As indicated on the flow sheet shown above, this can be accomplished by either direct oxidation, or by cleavage ofthe intermediate glycol (compound III).

In carrying out this conversion by the direct oxidation, the 2,4b-dimethyl-7-ethylenedioxy-2-methallyl-l-acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-one is dissolved in a suitable solvent, such as a lower aliphatic alcohol, the solution cooled to a low to perature of about C., and ozonized oxygen containing one equivalent of ozone based on the dodecahydrophenanthrene is passed through the solution. The resulting reaction mixture is warmed to about 0 C. and the ozonide decomposed in accordance with methods known in the art, as for example, by reduction with a small amount of zinc and aqueous acetic acid. After decomposition of the ozonide, the product 2,4b-dimethyl- 7-ethylenedioxy 2([3-ketopropyl)-l-acetaldehydo-1,2,3. 4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-4-one is readily recovered by concentrating the reaction mixture under diminished pressure, extracting the concentrate with ether, chromatographing the concentrate over acid washed alumina, eluting with a mixture of petroleum ether-ethyl ether, and evaporating the resulting eluate.

droxy 2O keto pregnene.

Alternatively, and in accordance with atpreferred embodiment of our invention, the l3-ketopropyl compound is obtained :by a two stepprccess involving treating the methallyl compound with osmiumtetroxide and decomposing the resulting osmate ester to produce the corresponding 2-(fi,'y-dihydroxyisobutyl) compound, and cleaving this latter product by treatment with periodic acid. In this procedure, the 2,4b-dimethyl-7-ethylenedioxy-2- ,methallyl l acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a- ,dodecahydrophenanthrene-4-one is reactedwith osmium .tetroxide to form the corresponding osmate ester, the re- .action being preferably effected in a suitable inert solvent .medium such as benzene, ethyl ether, tetrahydrofuran, .;and the like, r in a mixture of such solvents. The reaction is completed by allowing the reaction mixture to ;stand at room temperature for about one hour. .osmate ester is then decomposed by adding ethanol and treating theresulting solution with an aqueous solution of The sodium sulfite. The glycol formed in this reaction-mix- ..ture .can be recovered by filtering the resulting reaction mixture, concentrating this solution under diminished pressure, extracting this concentrate with chloroform, and evaporating the chloroform extract.

The 2,4b dimethyl-7-ethylenedioxy-2-(,Bq-dihydroxyisobutyl) 1 acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-0ne is then conveniently converted to the corresponding 2-(,8-ketopropyl) compound by reacting a solution of this product in a mixture of tetrahydrofuran and pyridine with a solution of periodic acid and allowing the. resulting reaction mixture to stand at about room temperature for about one-half ,hour. At this point, the mixture is diluted with water and -1he tetrahydrofuran removed by concentration under ,;diminished pressure.

;extractedwith benzene and the 2,4b-dimethyl-7-ethylenc- .dioxy 2 (B -vketopropyl)-1-acetaldehydo-1,2,3,4,4a,4b,

Theresulting concentrate is then 5,,6,7,8, l0,10a-dodecahydrophenanthrene-4-one obtained by concentration of the benzene extracts.

The Z-(B-ketopropyl) compound is then reacted with .an alkaline reagent to efiect ring closure .and formthe corresponding steroid compound. Thus, onheating a .vertibleto keto by hydrolysis with acid, obtained in vaccordance with the present invention are ,valuable com- [pounds useful as intermediates in the synthesis of :cortisone. Thus, for example, dl-A -3-ethylenedi0xypregnadiene-11,20-dione can be selectively hydrogenated by reaction with hydrogen in the presence of Raney nickel catalyst to produce dl-A -3-ethylenedioxy-pregnene- 11,20-dione by the method shown Berichte 72, 182 for reducing Ai -3-hydroxy-2O-keto pregnadiene to A -3-hy- The dl-A -3-ethylenedioxypregnene-l1,20-dione can then be converted to cortisone .by the methods described in the Journal of the American Chemical Society 74, 4974 (1952).

The 2,4b-dimethyl-1-(B-hydroxyethyl) -2-methallyl-7- .ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydro- .phenanthrene-4-0l used as the starting material in the examples illustrating the processes of this invention, can be prepared as described in copending application, Serial No. 310,134, filed September 17, 1952.

. d EXAMPLE 1 2,415 dimethyl 7 ethylenedioxy-Z-methallyl-l-acetaldehydo) ],2,3,4,4a,4b,5,6,7,8,10,10a dodecahyarophenanthrene-4on2 To the complex from 380 mg. of chromium trioxide dissolved in 3.5 cc. of pyridine was added 384 mg. of 2,4b dimethyl-7-ethylenedioxy-Z-methallyl-1-(fi-hydroxyethyl) 1,2,3,4,4a.4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-ol in 3 cc. of pyridine. After standing over night at room temperature, ,thereaction mixturevwas diluted with water. and extracted with ether. The combined ether extracts were washed with water, driedand concentrated. The resulting crude crystalline product was chromatographed on 12 g. of acidwashed alumina. -With petroleum ether-ether there was eluted first 2,4bdimethyl 7 ethylenedioxy Z-methallyl-l-acetaldehydo- 1,2,3,4,4a,4b,5,6,7,8,10,1.0a. .dodecahydrophenanthrene 4-onemelting at.148-150 C. after recrystallization from ether followed by 2,4b dimethyl 7 ethylenedioxy 2- methallyl 1 ,(fi-hydroxyethyl)-1,2,3,4,4a,4b,5,6,7,8,10,

v10a-dodecahydrophenantl1rene-4-one, M. P. l82-6 C.

from ether. Further .elutionwith methanol gave 2,411- dimethyl 7 ethylenedioxy-Z-methallyl-l-carboxymethyl- 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4- one melting at 215-216 C. after purification by recrystallization from ethyl acetate. I

"The above 1 -(-/3-hydroxyethyl) .compound and the 1- (carboxymethyl) compound may be, reduced with lithium aluminum hydride in tetrahydrofuran to produce the C-11 ;epimer of 2,.4b dimethyl 7-ethylenedioxy-2-rnethallyl-1- .(p hydroxyethyl) 1,2,3,4,4a,-4b,5,6,7,8,10,10a-dodeca- .hydrophenanthrenel-ol, the original starting material.

The 2,4b-dimethyl-7-ethylenedioxy-2-methallyl-l-acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophe- 'nanthrene-4-one on acid hydrolysis yields 2,4b-dimethyl-2- .methallyl- 1 acetaldehydo 1,2,3,4,4a,4b,5,6,7,-8,10,10a-

dodecahydrophenanthrene-4,7-dione.

Similarly, on acid hydrolysis 2,4b-dimethyl-7-ethylen dioxy 2 methallyl-l-(fi-hydroxyethyl)-l,2,3,4,4a,4b,5, 6,7,8,10,10a-dodecahydrophenanthrene-4-one and 2,4bdimethyl 7 ethylenedioxy-Z-methallyl-1 carboxymethyl- 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene- 3 4 one yields 2,4b-dimethyl2-methallyl-1-(fl-hydroxyethyl) l,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydi'ophenanthrene 4,7 dime and 2,4b-dimethy1-2-methallyl-1- carboxymethyl 1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene-4,7-dione respectively.

EXAMPLE 2 2,4b dimethyl 7 ethylenedioxy-Z-merhallyl-1-carb0xymethyl ],2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-one In another experiment carried out as described in Example 1, the combined ether extracts were extracted with aqueous sodium hydroxide solution at this point to remove the carboxymethyl compound before chromatographing the mixture. The sodium hydroxide extract was then acidified with aqueous sodium dihydrogen phosphate solu tion whereupon crystalline 2,4b-dimethyl-7-ethylenedioxy- 2 methallyl-1-carboxymethyl-1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene 4-one separated from the sold tion.

Chromatography of the ether extracts was then carried out as described in Example 1 with the exception that the methanol elution was omitted.

EXAMPLE 3 2,4b-dimethyl-7-ethylenedioxy-2-(Bq-dihydroxyisobutyl)- I-acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydr0phenanthrene-4-0ne To a solution of mg. of 2,4b-dirnethyl-7-ethylenedioxy 2 methallyl 1' acetaldehydo 1,2,3,4,4a,4b,5,-

7 6,7.8,10,lOa-dodccahydrophenanthrenet-one in 1.5 cc. of benzene and 0.5 cc. of tetrahydrofuran was added 110 mg. of osmium tetroxide. After one hour at room temperature the precipitated osmate ester was dissolved in 6.5 cc. of ethanol and treated with a solution of 700 mg. of sodium sulfite in 4 cc. of water. The mixture was agitated thoroughly for twenty minutes to effect hydrolysis of the-osmate ester. After standing briefly the upper layer was decanted and the lower layer was washed repeatedly by decantation with ethanol. The organic solutions were combined and concentrated to a small volume. Extraction with chloroform followed by washing with water, drying and concentration yielded crystalline 2,4b-dimethyl-7-ethylenedioxy-2-(,3,'y-dihydroxyisobutyl) 1 acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-4-one, melting at 174-177 C. after purification by recrystallization from benzene.

Upon hydrolysis with acid, 2,4b-dimethyl-7-ethylenedioxy 2 (5,7-dihYdlOXYiSObUtYl) l acetaldehydo 1,2,- 3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 4- one is converted to 2,4b-dimethyl-2-(fl;y-dihydroxyisobutyl) 1 acetaldehydo l,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-4,7-dione.

EXAMPLE 4 2,4b dimethyl 7 ethylenedioxy 2 (,8 ketopropyD- 1 acetaldehydo 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrphenanthrene-4-one To 200 mg. of 2,4b-dimethyl-7-ethylenedioxy-2-(,8,'ydihydroxyisobutyl) 1 acetaldehydo l,2,3,4,4a,4b,5,6,-

' 7,8,10,10a-dodecahydrophenanthrene-4-one in 1.5 cc. of

. melted at 131l33 C. after being recrystallized from ether.

Upon hydrolysis with acid, 2,4b-dimethyl-7-ethy1eriedioxy 2 (/3 ketopropyl) l acetaldehydo 1,2,3,4,- 4a,4b,5,6,7,8,l0,10a-dodecahydrophenanthrene-4-one is converted to 2,4b-dimethyl-2- (fi-ketopropyl)-l-acetaldehydo l,2,3,4,4a,4b,5,6,7,9,10,1021 dodecahydrophenanthrene-4,7-dione.

EXAMPLE 5 dl-A -3-ethylenedioxy-pregnadiene-I1 ,ZO-dione concentrated. The residue was recrystallized from ether giving dl-A -3-ethylenedio xy-pregnadiene-11,2O-dione melting at 193-197 C.

When A -3-ethylenedioxy-pregnadiene-l1,20-dione is hydrolyzed by treatment with acid, n -pregnadiene- 3,11,20-trione is obtained.

Various changes and modifications in the procedure herein disclosed will occur to those skilled in the art, and

to the extent that such changes and modifications are embraced by the appended claims, it is to be understood that they constitute part of our invention.

We claim: 7

l. The process which comprises intimately contacting 2,4b-dimethyl-1-(p-hydroxyethyl) -2-methallyl-7-ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene-4-ol'with pyridine-chromium trioxide complex to produce 2,4b dimethyl 1 acetaldehydo 2 methallyl- 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,1021 dodecahydrophenanthrene-4-one, reacting this compound with osmium tetroxide and decomposing the resulting osmate ester to obtain 2,4b-dimethyl-l-acetaldehydo-2-(fi -dihydroxyisohutyl) 7 ethylenedioxy l,2,3,4,4a,4b,5,6,7,- 8,10,lOa-dodecahydrophenanthrene-4-one, cleaving this compound by reaction with periodic acid to produce 2,4bdimethyl 1 acetaldehydo-2-({B-ketopropyl)-7-ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenantl1rene-4-one, reacting this compound with potassium hydroxide to produce A 3-ethylenedioxy-pregnadiene- 11,20-dione, and hydrolyzing this product by heating with acid to obtain A -pregnadiene-3,l1,20-trione.

2. The process which comprises intimately contacting a compound of the formula wherein R represents a group convertible to keto by acid hydrolysis and R represents a member from the group consisting of keto and hydroxyl, with an oxidizing agent to produce the corresponding l-acetaldehydo-4-keto compound, reacting this compound with osmium tetroxide and decomposing the resulting osmate ester to obtain the corresponding l-acetaldehydo-2-(fi,'y-dihydroxyisobutyl)- 4-keto compound, cleaving this compound by reaction with periodic acid to produce the corresponding l-acetaldehydo-Z-(,B-ketopropyl)-4-keto compound, reacting this product with an alkaline reagent to produce a pregnadiene of the formula and hydrolyzing this compound by heating with acidto produce A -pregnadiene-3J1,2O-trione. 3. The process which comprises intimately'contacting 2,4b dimethyl- 1 (B hydroxyethyl) 2 methallyl 7- ethylenedioxy l,2,3,4,4a,4b,5,6,7,8,10,l0a dodecahydrophenanthrene-4-ol with pyridine-chromium trioxide complex to produce 2,4b-dimethyl-1-acetaldehydo-Z-methallyl- 7 ethylenedioxy l,2,3,4,4a,4b,5,6,7,8,10,10a dodecahy drophenanthrenet-one, reacting this compound with osmium tetroxide and decomposing the resulting osmate ester to obtain 2,4b-dimethyl-l-acetaldehydo-2-(fl -dihydroxyisobntyl) 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,- 8,10,l0a-dodecahydrophenanthrene-4-one oxidizing this compound -by reaction with periodic acid to produce 2,4b dimethyl 1 acetaldehydo 2 (,8 ketopropyD 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrenet-one, and reacting this compound with potassium hydroxide to produce A -B-ethyIenedioxy-pregnadiene-l1,20-dione.

9 10 4. The process which comprises intimately contacting 5. The process which comprises reacting 2,4b-ditnethyl; a compound of the formula 1 acetaldehydo 2 (fifketopropyl) 7 ethylenedioxy- CH3 7 1,2,3,4,4a,4b,5,6,7,8,10,102. dodecahydrophenanthrene- 4-one with potassium hydroxide to produce A -3-ethyl- H3 020E enedioxy-pregnadiene-l1,20-dione. Rr- --CH2 6. The process which comprises reacting a compound of CH3 the formula -CH2CH2OH (3H3 CH3 3 R- O- --CH2 CH3 wherein R represents a group convertible to a keto by OH2CHO acid hydrolysis, and R represents a member from the group consisting of keto and hydroxyl, with an oxidizing agent to produce the corresponding 1-acetaldehydo-4-keto R- compound, reacting this compound With osmium tetroxide and the resnltmg Osmate ester to Qbtam the wherein R represents a group convertible to keto by acid correspondmg 1'acetaldshydo'z"(fifl'dlhydmxylsobutyl)' hydrolysis with an alkaline reagent to produce a com- 4-keto compound, cleaving this compound by reaction pound of the formula with periodic acid to produce the corresponding l-acetaldehydo-2-(B-ketopropyl) -4-keto compound, and reacting this product with an alkaline reagent to produce a pregnadiene of the formula 0:0

CH3 I on Y 0 (i=0 CH3 O CH3 R 7. A -3-ethylenedioxy-pregnadiene-1 1,20-dione.

R No references cited. 

1. THE PROCESS WHICH COMPRISES INTIMATELY CONTACTING 2,4B-DIMETHYL-1-(BHYDROXYETHYL)-2-METHALLYL-7-ETHYLENEDIOXY -1,2,3,4,4A,4B,5,6,7,8,10,10A - DODECAHYDROHENANTHRENE-4-OL WITH PYRIDINE-CHROMIUM TRIOXIDE COMPLEX TO PRODUCE 2,4B - DIMETHYL - 1 -ACETALDEHYDRO - 2 - METHALLYL7 - ETHYLEMEDIOXY - 1,2,3,4,4A,4B,5,6,7,8,10,10A - DODECAHYDRPJENANTHRENE-4-ONE, REACTING THIS COMPOUND WITH OSMIUM TETROXIDE AND DECOMPOSING THE RESULTING OSMATE ESTER TO OBTAIN 2,4-DIMETHYL-1-ACETALDEHYDO-2-(B,Y-DIHYDOXYISOBUTYL) - 7 - ETHYLENEDIOXY - 1,2,3,4,4A,4B,5,6,7,1,10,10A-DODECAHYDROPHENANTHRENE-4-ONE, CLEAVING THIS COMPOUND BY REACTION WITH PERIODIC ACID TO PRODUCE 2,4BDIMETHYL - 1- ACETALDEHYDO-2-(B-KETOPROPYL)-7-ETHYLENEDIOXY - 1,2,3,4,4A,4B,5,6,7,8,10,10A - DODECAHYDROPHENANTHRENE-4-ONE, REACTING THIS COMPOUND WITH POTASSIUM HYDROXIDE TO PRODUCE 5,16-3-ETHYLNEDIOXY-PREGGNADIENE11,20-DIONE, AND HYDROLYZING THIS PRODUCT BY HEATING WITH ACID TO OBTAIN 4,16-PREGNADIENE-3,11,20-TRIONE. 